In recent literature, the fragility index (FI) has been used to evaluate the robustness of statistically significant findings of dichotomous outcomes. This metric is defined as the minimum number of outcome events to flip study conclusions from significant to nonsignificant. Orthopaedics literature is frequently found to be fragile with a median FI of 2 in 150 RCTs across spine, hand, sports medicine, trauma and orthopaedic oncology studies. While many papers discuss limitations of FI, we aimed to further characterize it by introducing the Fragility Likelihood (FL), a new metric that allows us to consider the probability of the event to occur and to calculate the likelihood of this fragility to be reached.

We systematically reviewed all randomized controlled trials in the Journal of Bone and Joint Surgery (Am) over 10 years. The FL was calculated with the following formula: A x B x C x 100% (A= FI; B = probability of the event in the group with the smallest number of events; C= probability of the non-event in the group with the highest number of events). A smaller FL demonstrates more robust results and conversely, a larger FL illustrates a higher likelihood of fragility being reached and more fragile the findings.

The median FI for the statistically significant outcomes was 2 (Mean: 3.8; Range 0-23). The median FL for the statistically significant outcomes was 11% (Mean: 22%, Range: 2%-73%). This means that the probability of reaching non-significance is only 11% when considering the probability of the event to occur. When comparing studies with the same FI we found the FL to range from 3% to 43%. This illustrates the large differences in robustness between trials with equal FI when the likelihood of the event was taken into consideration.

As orthopaedic studies are frequently reported as fragile, we found that by calculating the FL, studies may be more robust than previously assumed based off FI alone. By using the FL in conjunction with FI and p-values will provide additional insight into the robustness of the reported outcomes. Our results indicate that by calculating the FL, study conclusions are stronger than what the FI alone predicts. Although conducting RCTs in surgery can be challenging, we must endeavor to critically evaluate our results so we can answer important orthopaedic questions with certainty.

Non-invasive sampling of tumor-derived genetic material in circulation through liquid biopsy may be very beneficial for an accurate diagnosis and evaluation of response to treatment in patients with malignant and benign soft tissue tumors. We previously showed that tumor-derived genomic aberrations can be detected in plasma of patients with leiomyosarcoma (LMS) and leiomyoma (LM). In LMS patients, we also showed that the levels of circulating tumor DNA (ctDNA) correspond with response to treatment. We developed an approach tailored to genomic profile of LMS (characterized by intermediate levels of point mutations and copy number alterations, CNAs). Based on TCGA data, we designed a panel of 89 most frequently mutated genes in LMS, which we profiled in plasma DNA by deep sequencing. In parallel, plasma samples were analyzed by shallow whole genome sequencing for detection of CNAs. With this approach, we detected ctDNA in 71% (20/28) of samples from 6/7 patients with advanced disease with >98% specificity. The combination approach for orthogonal profiling of point mutations and CNAs proved to increase the sensitivity of ctDNA detection. Currently, we seek to further improve the sensitivity of ctDNA detection by refining our capture panel and tracking LMS-specific DNA methylation markers in circulation, in addition to point mutations and CNAs. The ultimate goals of our ctDNA studies are 1) to develop a highly sensitive assay for evaluation of response to therapy and long-term surveillance for patients with LMS, and 2) to develop a blood-based test for accurate pre-operative distinction between LMS and LM.

To identify LMS-specific DNA methylation markers, we analyzed a test cohort of 76 LM, 35 uterine LMS and 31 extra-uterine LMS by Illumina Infinium EPIC arrays. We identified differentially methylated CpGs between LM and uterine LMS, and between LM and all LMS using a newly developed custom pipeline in R. The results of this analysis are currently being validated in a new dataset of 41 LM and 153 LMS generated by our group. Recently published (PMID: 34301934) genomic data from new 53 LMS samples are used to refine the panel of the most frequently mutated genes that we identified previously in the LMS TCGA data.

Our preliminary analysis of test cohort revealed >270 differentially methylated CpGs between LM and uterine LMS, and >1000 differentially methylated CpGs between LM and all LMS. The preliminary analysis of genomic data shows that the initial panel of 89 frequently mutated genes could be substantially narrowed down to cover only selected tumor suppressor genes. Once validated, these results will be used to refine the ctDNA assay for LMS and LM.

Our results point to multiple epigenetic markers that could be used for ctDNA profiling, in addition to point mutations or CNAs. Further validation will allow us to select the most reliable LMS- and LM-specific DNA methylation markers and the most frequently mutated regions across independent datasets, and these markers will be incorporated into our new ctDNA test for a concurrent detection of point mutations, CNAs and DNA methylation markers in circulation.

The reconstruction of peri-acetabular defects after severe bone loss or pelvic resection for tumor is among the most challenging surgical intervention. The Lumic® prosthesis (Implantcast, Buxtehude, Germany) was first introduced in 2008 in an effort to reduce the mechanical complications encountered with the classic peri-acetabular reconstruction techniques and to improve functional outcomes. Few have evaluated the results associated with the use of this recent implant.

A retrospective study from five Orthopedic Oncology Canadian centers was conducted. Every patient in whom a Lumic® endoprosthesis was used for reconstruction after peri-acetabular resection or severe bone loss with a minimal follow-up of three months was included. The charts were reviewed and data concerning patients’ demographics, peri-operative characteristics and post-operative complications was collected. Surgical and functional outcomes were also assessed.

Sixteen patients, 11 males and five females, were included and were followed for 28 months [3 – 60]. Mean age was 55 [17–86], and mean BMI reached 28 [19.6 – 44]. Twelve patients (75%) had a Lumic® after a resection of a primary sarcoma, two following pelvic metastasis, one for a benign tumor and one after a comminuted acetabular fracture with bone loss. Twelve patients (75%) had their surgery performed in one stage whereas four had a planned two-stage procedure. Mean surgical time was 555 minutes [173-1230] and blood loss averaged 2100 mL [500-5000]. MSTS score mean was 60.3 preoperatively [37.1 – 97] and 54.3 postoperatively [17.1-88.6]. Five patients (31.3%) had a cemented Lumic® stem. All patients got the dual mobility bearing, and 10 patients (62.5%) had the largest acetabular cup implanted (60 mm). In seven of these 10 patients the silver coated implant was used to minimize risk of infection. Five patients (31.3%) underwent capsular reconstruction using a synthetic fabric aiming to reduce the dislocation risk. Five patients had per-operative complications (31.3%), four were minor and one was serious (comminuted iliac bone fracture requiring internal fixation). Four patients dislocated within a month post-operatively and one additional patient sustained a dislocation one year post-operatively. Eight patients (50%) had a post-operative surgical site infection. All four patients who had a two-stage surgery had an infection. Ten patients (62.5%) needed a reoperation (two for fabric insertion, five for wash-outs, and three for implant exchange/removal). One patient (6.3%) had a septic loosening three years after surgery. At the time of data collection, 13 patients (81.3%) were alive with nine free of disease. Silver coating was not found to reduce infection risk (p=0.2) and capsuloplasty did not prevent dislocation (p=1).

These results are comparable to the sparse data published. Lumic® endoprosthesis is therefore shown to provide good functional outcomes and low rates of loosening on short to medium term follow-up. Infection and dislocation are common complications but we were unable to show benefits of capsuloplasty and of the use of silver coated implants. Larger series and longer follow-ups are needed.

Resection of the proximal femur raises several challenges to the orthopedic oncology surgeon. Among these is the re-establishment of the abductor mechanism that might impacts on hip function. Extent of tumor resection and surgeons’ preferences dictate the reconstruction method of the abductors. While some surgeons advocate the necessity of greater trochanter (GT) preservation whenever possible, others attempt direct soft tissues reattachment to the prosthesis. Sparse data in the literature evaluated the outcomes of greater trochanter fixation to the proximal femur megaprosthesis.

This is a retrospective monocentric study. All patients who received a proximal femoral replacement after tumor resection between 2005 and 2021 with a minimum follow-up of three months were included. Patients were divided into two groups: (1) those with preserved GT reattached to the megaprosthesis and (2) those with direct or indirect (tenodesis to fascia lata) abductor muscles reattachment. Both groups were compared for surgical outcomes (dislocation and revision rates) and functional outcomes (Trendelenburg gait, use of walking-assistive device and abductor muscle strength). Additionally patients in group 1 were subdivided into patients who received GT reinsertion using a grip and cables and those who got direct GT reinsertion using suture materials and studied for GT displacement at three, six and 12 months. Time to cable rupture was recorded and analyzed through a survival analysis.

Fifty-six patients were included in this study with a mean follow-up of 45 months (3-180). There were 23 patients with reinserted GT (group 1) and 33 patients with soft tissue repair (group 2). Revision rate was comparable between both groups(p=0.23); however, there were more dislocations in group 2 (0/23 vs 6/33; p=0.037). Functional outcomes were comparable, with 78% of patients in group 1 (18/23) and 73% of patients in group 2 (24/33) that displayed a Trendelenburg gait (p=0.76). In group 1, 70% (16/23) used walking aids compared to 79% of group 2 (27/33) (p=0.34). Mean abductor strength reached 2.7 in group 1 compared to 2.3 in group 2 (p=0.06). In group 1, 16 of the 23 patients had GT reinsertion with grip and cables. Median survival of cables for these 16 patients reached 13 months in our series. GT displacement reached a mean of two mm, three mm, and 11 mm respectively at three, six and 12 months of follow-up in patients with grip and cables compared to 12 mm, 24 mm and 26 mm respectively at the same follow-up intervals in patients with GT stand-alone suture reinsertion(p<0.05).

Although GT preservation and reinsertion did not improve functional outcomes after proximal femur resection and reconstruction with a megaprosthesis, it was significantly associated with lower dislocation rate despite frequent cable failure and secondary GT migration. No cable or grip revision or removal was recorded. Significantly less displacement was observed in patients for whom GT reattachment used plate and cables rather than sutures only. Therefore we suggest that GT should be preserved and reattached whenever possible and that GT reinsertion benefits from strong materials such as grip and cables.

The reconstruction of peri-acetabular defects after severe bone loss or pelvic resection for tumor is among the most challenging surgical intervention. The Lumic® prosthesis (Implantcast, Buxtehude, Germany) was first introduced in 2008 in an effort to reduce the mechanical complications encountered with the classic peri-acetabular reconstruction techniques and to improve functional outcomes. Few have evaluated the results associated with the use of this recent implant.

A retrospective study from five Orthopedic Oncology Canadian centers was conducted. Every patient in whom a Lumic® endoprosthesis was used for reconstruction after peri-acetabular resection or severe bone loss with a minimal follow-up of three months was included. The charts were reviewed and data concerning patients’ demographics, peri-operative characteristics and post-operative complications was collected. Surgical and functional outcomes were also assessed.

Sixteen patients, 11 males and five females, were included and were followed for 28 months [3 – 60]. Mean age was 55 [17-86], and mean BMI reached 28 [19.6 – 44]. Twelve patients (75%) had a Lumic® after a resection of a primary sarcoma, two following pelvic metastasis, one for a benign tumor and one after a comminuted acetabular fracture with bone loss. Twelve patients (75%) had their surgery performed in one stage whereas four had a planned two-stage procedure. Mean surgical time was 555 minutes [173-1230] and blood loss averaged 2100 mL [500-5000]. MSTS score mean was 60.3 preoperatively [37.1 – 97] and 54.3 postoperatively [17.1-88.6]. Five patients (31.3%) had a cemented Lumic® stem. All patients got the dual mobility bearing, and 10 patients (62.5%) had the largest acetabular cup implanted (60 mm). In seven of these 10 patients the silver coated implant was used to minimize risk of infection. Five patients (31.3%) underwent capsular reconstruction using a synthetic fabric aiming to reduce the dislocation risk. Five patients had per-operative complications (31.3%), four were minor and one was serious (comminuted iliac bone fracture requiring internal fixation). Four patients dislocated within a month post-operatively and one additional patient sustained a dislocation one year post-operatively. Eight patients (50%) had a post-operative surgical site infection. All four patients who had a two-stage surgery had an infection. Ten patients (62.5%) needed a reoperation (two for fabric insertion, five for wash-outs, and three for implant exchange/removal). One patient (6.3%) had a septic loosening three years after surgery. At the time of data collection, 13 patients (81.3%) were alive with nine free of disease. Silver coating was not found to reduce infection risk (p=0.2) and capsuloplasty did not prevent dislocation (p=1).

These results are comparable to the sparse data published. Lumic® endoprosthesis is therefore shown to provide good functional outcomes and low rates of loosening on short to medium term follow-up. Infection and dislocation are common complications but we were unable to show benefits of capsuloplasty and of the use of silver coated implants. Larger series and longer follow-ups are needed.

Solitary fibrous tumor (SFT) is a rare mesenchymal tumor with an intermediate tendency to metastasize, which is found in many different locations including head and neck, abdomen, chest cavity and extremities. Also, meningeal hemangiopericytoma (HPC) is considered an SFT which arises in the meningeal membranes. SFT family shows an undetermined biologic behavior varying from a silent indolent tumor to an aggressive malignant form; however, benign and malignant variants of SFT may have similar cytopathologic characteristics. In this study, we defined the factors correlated with SFT's aggressive behavior and patient's survival.

This is a retrospective study based on medical records of 85 patients who were suffering from SFT and had been treated at McGill University Health Centre (MUHC) between 1984 and 2017. We used multivariate logistic regression analysis to address any association between the variables including patient's demographics, tumor size, primary location of the tumor, pathological features, treatment methods and outcomes.

The median of the follow-up period was 60 months. The patient's age or gender had no association with tumor aggressive behavior or patient's survival. Anatomical origin of primary tumor had no strong correlation with the patient's disease related death (DRD); however, tumors originated from CNS showed more aggressive behavior. There was an association between tumor size more than 7 cm and distant metastasis (MT) (p= 0.03) and DRD (p=0.03). The tumor size also correlated with the 5-year disease-free survival (p=0.017). We had three histologic groups: 1- Benign SFT (30 cases), 2- cellular SFT or HPC (29 cases), 3- malignant SFT or anaplastic HPC (26 cases). Although univariate analysis demonstrates that patients suffering from cellular SFT and malignant SFT showed increased aggressive behavior of the tumor, multivariate analysis didn't verify the mentioned association. Patients with positive margins had increased odds ratio to experience tumor local recurrence (LR) (p= 0.05) and LR was correlated with DRD in our patients (p=0.006). Radiotherapy had no statistical association with LR, MT or DRD. Frequency of LR and MT in the study were 25.7% and 29.8% respectively. 5-year disease-free survival in our patients was 76%.

The size of SFT is the most correlative predictor of the tumor's aggressive behavior. The local recurrence of SFT is associated with disease related death; therefore, resection of the tumor with negative margins provides the highest chance of cure. In addition, a cellular SFT should be treated like a malignant variant of the tumor.

The aim was to analyze the efficacy of zoledronic acid (ZA) versus denosumab in the prevention of pathological fractures in patients with bone metastases from advanced cancers by evaluating all available randomized controlled trials (RCTs) on this subject.

A systematic search of electronic databases (PubMed and MEDLINE) was performed to identify all published RCTs comparing zoledronic acid with denosumab in prevention of pathological fractures in bone metastases. Risk of bias of the studies was assessed. The primary outcomes evaluated were pathological fractures.

Four RCTs (7320 patients) were included. Denosumab was superior to ZA in reducing the likelihood of pathological fractures, when all tumour types were combined (OR 0.86, 95% CI [0.74, 0.99], p = 0.04). Denosumab was not significantly favoured over ZA in endodermal origin (breast and prostate) (OR 0.85, 95% CI [0.68, 1.05], p = 0.13) and mesodermal origin tumours (solid tumours and MM) (OR 0.87, 95% CI [0.71, 1.06], p = 0.16).

Denosumab significantly reduces the likelihood of pathological fractures in comparison to ZA in patients with bone metastases. When pathological fractures were grouped by tumour origin (endodermal or mesodermal), there was no significant difference between denosumab and ZA. Further long-term studies are needed to confirm the effectiveness of these treatment regimens.

The patient's subjective experience of disease is an increasing focus in health care delivery. Health-related quality of life (HRQoL) is defined as a “functional effect of a medical condition and its consequent treatment”; it is both self-reported and multi-dimensional. While functional outcome is well researched among the soft tissue sarcoma (STS) population, few studies have focused on HRQoL, which gives a broader understanding of the psychological, somatic, social and physical toll of cancer and its treatment from the patient's viewpoint. The biologic and anatomic heterogeneity of sarcomas are considerable, just as the treatments are diverse, we surmise that the indicators of patient HRQoL differ and are not captured in existing generic HRQoL tools for cancer. The study objectives were to explore the domains of HRQoL and functioning in adult patients diagnosed with extremity STS from the patient's perspective from active care through survivorship through qualitative inquiry, so as to form the basis for the development of a patient-derived, sarcoma-specific, preference based HRQoL tool.

Study design is a sequential exploratory mixed methods study of patient experience in localized or metastatic adult extremity STS (2007 and 2017). The study was conducted at a high-volume sarcoma centre. Qualitative descriptive design was grounded in an integrated knowledge translation approach and aimed at identifying HRQoL domains through in-person and electronic focus groups, and individual semi-structured interviews in both English and French (N=28). The interview guide topics were selected based on existing knowledge about PROs and HRQoL life, including (a) impact of diagnosis on employment or acquisition of academic/vocational skills; (b) physical and psychological functioning; (c) symptom burden; (d) treatment preferences; (e) knowledge of and use of existing resources; (f) impact on family time and resources; and (g) overall experience. Data was analyzed using inductive thematic networks approach using the qualitative software N-Vivo 12. Codes were generated by 2 independent qualitative experts capturing key concepts of HRQoL that is impacted by STS. Basic themes were clustered into organizing themes, and merged into global domains. Attention was paid to deviant cases and within-group dynamics during focus group discussion analysis. Discrepancies or inconsistencies in coding were resolved in consensus meetings. Final sample size was determined when data saturation was reached and no new themes emerged. Qualitative reduction of identified items to reach a consensus framework was facilitated by a moderator during multi-disciplinary panel meetings comprised of sarcoma experts, patient partners, allied health staff and other stakeholders.

Twenty-nine patients with biopsy-proven localized or metastatic STS of the extremity participated (69% lower extremity STS; mean age 56 years, 25% with local recurrence, 21% metastatic, 18% amputation). Inductive thematic network analysis revealed five function-related domains HRQoL for patients with STS. The functional domains were mapped to the Wilson & Cleary Model and experience domains were mapped to the Picker Institute's Through Patient's Eyes model.

This is a critical step toward developing disease specific outcome measures. Patient-centered research is crucial to understanding the impact of surgery, adjuvant therapy and the associated complications for patients with extremity STS, and thereby improving the quality of care provision. This study offers a unique perspective on what domains and sub domains are most impactful on HRQoL and provides the basis for our on-going development of a disease-specific, preference-based HRQoL measure.

The use of endoprosthesis implants is frequent for tumours involving the proximal third of the femur and not amenable to primary arthroplasty or internal fixation. In this population, these implants are preferentially cemented given poor bone quality associated with systemic diseases and treatments. Loosening is a common complication of these implants that have been linked to poor bone quality, type of implants and importantly cementing technique. Thus, these techniques vary between different surgeons and based mainly on previous experience. One of the most successful cementing techniques in the arthroplasty literature is the French paradox. This technique involves removing the cancellous bone of the proximal femoral metaphysis and selects the largest stem to tightly fit the created cavity delineated by cortical bone. Cementing the implant results in a very thin cement layer that fills the inconsistent gaps between the metal and the bone. To our knowledge, no previous report exists in the literature assessing loosening in proximal femur replacement using the French paradox cementing technique. In this study, we sought to examine (1) rates of loosening in proximal femur replacement, and (2) the oncological outcomes including tumour recurrence and implant related complications.

A retrospective study of 42 patients underwent proximal femur replacement between 1990 and 2018 at our institution. Of these, 30 patients met our inclusion criteria. Two independent reviewers have evaluated the preoperative and the most recent postoperative radiographs using the International Society of Limb Salvage (ISOLS) radiographic scoring system and Gruen classification for femoral stem loosening. Additionally, the acetabulum was evaluated for erosion according to the criteria of Baker et al. The mean age of this cohort was 60.5 (19–80), with 60% being males. The primary origin was metastatic in 17 (56.7%) patients, bone sarcoma in 10 (33.3%) patients and soft tissue sarcoma in 3 (10%) patients. Pathological fractures were present in 11 (36.7%) patients. Seven (23.3%) patients had prior intramedullary nailing. Preoperative radiotherapy was used in 8 (26.7%) and postoperative radiotherapy in 17 (56.7%) patients. The mean clinical follow-up was 25.2±26.3 months and the mean radiographical follow-up was 24.8±26 months.

The mean ISOLS score for both reviewers was found to be 89±6.5% and 86.5±6.1%, respectively. Additionally, the first reviewer found two patients to be possibly loos (6.7%) compared to one (3.3%) patient for the second reviewer. No components scored as probably or definitely loose and non-required revision for either loosening or metal failure. Furthermore, both reviewers showed no acetabular erosion in 25 (83.3%) and 24 (80%) patients, respectively. On the other hand, the overall rate of complications was 36.6% with 11 complications reported in 30 patients. Local recurrence occurred in five (16.6%) patients. Prosthetic Dislocation was the most frequent complications with eight dislocations in four patients.

Despite complications, our results showed no radiographic evidence of stem loosening. Cementing proximal femur prosthesis with a tight canal fit and with a thin cement mantle appears to be a viable option at short and medium term.

This study explored psychological functioning and coping styles in adult patients with localized and metastatic extremity soft-tissue sarcoma (STS) from diagnosis through survivorship in a single expert sarcoma center in Canada. Our analyses were driven by three main goals: 1) to develop a better understanding of the affective responses and coping mechanisms in patients who face this rare illness, 2) to identify areas of psychological functioning in which patients with STS experience most difficulties, and 3) to describe how these areas could be best addressed in clinical settings.

This descriptive qualitative study is a part of a larger mixed-methods study on health related quality of life (HRQoL) in adult patients with soft-tissue sarcoma treated between 2003 and 2018. Purposive sampling based on demographic and disease variables from all patients within a prospective database was utilized to ensure a representative patient population. Three formats of data collection were conducted in French and English, 2 online focus groups (total n=12), 2 in-person focus groups (total n=12), as well as individual semi-structured interviews (n=4). Data was analyzed using inductive thematic networks approach using the qualitative software N-Vivo 12. Codes were generated by 2 independent qualitative experts that captured key concepts referring to psychological functioning and coping mechanisms. Basic themes were clustered into organizing themes, which were later merged into a global theme. Attention was paid to deviant cases, and within-group dynamics during focus group discussion analysis. Any discrepancies or inconsistencies in coding were resolved in a consensus meeting. The final sample size was determined when data saturation was reached, and no new themes emerged.

Our analyses of psychological well-being and functioning revealed three main themes, mood, anxiety, and body image concerns. Feelings of depression and low mood were prominent, coinciding with physical symptoms and limitations especially during the phase of treatment and recovery. Women were more likely to report emotional volatility, while men tended to report more preoccupation. Loss of control and independence, anxiety related to illness recurrence, uncertainty about the future and facing one's mortality significantly impacted quality of life. Furthermore, while patients were more concerned with limb functionality, disfigurement and self-consciousness featured prominently in the narrative. Four adaptive coping styles were observed, positive reframing and optimism, finding a purpose, being proactive, and using humor. Among the maladaptive strategies, we noted passive acceptance, and avoidance and denial.

Psychological well-being is an important domain in the HRQoL of adult patients with extremity STS. Physicians and medical workers should encourage adaptive coping mechanisms such as positive reframing and optimism. Patients endorsing higher levels of psychological distress and maladaptive coping styles should be monitored for their well-being and multidisciplinary strategies employed to optimize psychological function and HRQoL.

This is quite an innovative study that should lead to a multicentre validation trial. We have developed an FDG-PET/MRI texture-based model for the prediction of lung metastases (LM) in newly diagnosed patients with soft-tissue sarcomas (STSs) using retrospective analysis. In this work, we assess the model performance using a new prospective STS cohort. We also investigate whether incorporating hypoxia and perfusion biomarkers derived from FMISO-PET and DCE-MRI scans can further enhance the predictive power of the model.

A total of 66 patients with histologically confirmed STSs were used in this study and divided into two groups: a retrospective cohort of 51 patients (19 LM) used for training the model, and a prospective cohort of 15 patients (two patients with LM, one patient with bone metastases and suspicious lung nodules) for testing the model. In the training phase, a model of four texture features characterising tumour sub-region size and intensity heterogeneities was developed for LM prediction from pre-treatment FDG-PET and MRI scans (T1-weighted, T2-weighted with fat saturation) of the retrospective cohort, using imbalance-adjusted bootstrap statistical resampling and logistic regression multivariable modeling. In the testing phase, this multivariable model was applied to predict the distant metastasis status of the prospective cohort. The predictive power of the obtained model response was assessed using the area under the receiver-operating characteristic curve (AUC). In the exploratory phase of the study, we extracted two heterogeneity metrics from the prospective cohort: the area under the intensity-volume histogram of pre-treatment DCE-MRI volume transfer constant parametric maps and FMISO-PET hypoxia maps (AU-IVH-Ktrans, AU-IVH-FMISO). The impact of the addition of these two individual metrics to the texture-based model response obtained in the testing phase was first investigated using Spearman's correlation (rs), and lastly using logistic regression and leave-one-out cross-validation (LOO-CV) to account for overfitting bias.

First, the texture-based model reached an AUC of 0.94, a sensitivity of 1, a specificity of 0.83 and an accuracy of 0.87 when tested in the prospective cohort. In the exploratory phase, the addition of AU-IVH-FMISO did not improve predictive power, yielding a correlation of rs = −0.42 (p = 0.12) with lung metastases, and a relative change in validation AUC of 0% in comparison with the texture-based model response alone in LOO-CV experiments. In contrast, the addition of AU-IVH-Ktrans improved predictive power, yielding a correlation of rs = −0.54 (p = 0.04) with lung metastases, and a change in validation AUC of +10%.

Our results demonstrate that texture-based models extracted from pre-treatment FDG-PET and MRI anatomical scans could be successfully used to predict distant metastases in STS cancer. Our results also suggest that the addition of perfusion heterogeneity metrics may contribute to improving model prediction performance.

Wound complications are common in patients with soft tissue sarcomas (STS) treated with surgical excision. Limited data is available on predictive factors for wound complications beyond the relationship to neo-adjuvant or adjuvant radiotherapy. Likewise, the association between blood transfusion, patient comorbidities and post-operative outcomes is not well described. In the present study we identified the predictive factors for blood transfusion and wound complications in patients undergoing surgical resection of soft tissue sarcoma from a national cohort.

The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database was used to identify patients who underwent surgical resection of a STS from 2005 to 2013. Primary malignant soft tissue neoplasms were identified using the following ICD-9 codes: 171.2, 171.3 and 171.6. Patients treated with both wide excision and amputation were identified using the current procedural terminology (CPT) codes. Prolonged operative time was defined as greater than 90th percentile of time required per procedure. A multivariable logistic regression model was used to identify associations between patient factors and post-operative wound complications (superficial and deep surgical site infections (SSI), and wound dehiscence). A similar regression model sought to identify prognostic factors for blood transfusion and associations with post-operative outcomes.

A total of 788 patients met our inclusion criteria. Of theses, 64.2% had tumours in the lower limb, 23.1% patients had tumours in the upper limb, and 12.7% patients had pelvic tumours. Six hundred and forty patients (81.2%) underwent surgical excision; 148 (18.8%) patients had an amputation. Multivariable logistic regression modeling identified American Society of Anaesthesiologist (ASA) class 3 and 4 (OR=2.3, P=0.03; OR=8.3, P=0.001, respectively), amputation (OR=14.0, P<0.001) and prolonged operative time (OR=4.6, P<0.001) as significant predictors of blood transfusion. Radiotherapy (OR=2.6, P=0.01) and amputation (OR=2.6, P=0.01) were identified as predictors of superficial SSI, whereas ASA class 4 (OR=6.2, P=0.03), prolonged operative time (OR=3.9, P=0.012) and return to the operating room (OR=10.5, P<0.001) were associated with deep SSI. Male gender (OR=1.8, P=0.03), diabetes (OR=2.3, P=0.03), ASA class 3 (OR=2.4, P=0.003), amputation (OR=3.8, P<0.001) and steroids (OR=4.5, P=0.03) were identified as predictors for wound dehiscence and open SSI.

A national cohort demonstrates that male gender, diabetes, chronic steroid use, higher ASA score and radiotherapy are associated with an increased incidence of wound complications. One in twenty-three patients undergoing resection of an STS will require a blood transfusion, and this risk is correlated with amputation, prolonged operative time and increased ASA score. Strategies to decrease the risk of blood transfusion and wound complication should be considered for these patient groups.

Objectives

The diagnosis of surgical site infection following endoprosthetic reconstruction for bone tumours is frequently a subjective diagnosis. Large clinical trials use blinded Central Adjudication Committees (CACs) to minimise the variability and bias associated with assessing a clinical outcome. The aim of this study was to determine the level of inter-rater and intra-rater agreement in the diagnosis of surgical site infection in the context of a clinical trial.

Purpose

Due to the aging population, an increasing proportion of elderly patients with soft tissue sarcoma are presenting to cancer centers. This population appears to have a worse prognosis but the reasons for this has not been studied in depth. The purpose of this study is to examine the effect of age on the outcome of patients with extremity and trunk soft tissue sarcoma.

A retrospective review of our prospectively collected database was undertaken and the functional and oncologic outcomes after Type One pelvic resections for bone tumours of the ilium and sacrum were analyzed. Seventeen patients were identified with a minimum followup after resection of twelve months. In seven patients the bone defect was reconstructed, with no reconstruction in the remaining ten patients. The functional/oncologic outcomes of the two groups are similar, however patients without reconstruction had fewer complications and less dependence on walking aids suggesting that reconstruction may not be justified.

Management of defects created by Type One pelvic resections of large iliac bone tumours remains controversial. We reviewed the functional/oncologic outcome following resection with and without reconstruction.

Similar functional/oncologic outcome was achieved in both groups suggesting that reconstruction is not justified.

A retrospective review of our prospectively collected database was undertaken analyzing functional/oncological outcome of seventeen patients with Type One pelvic resection. Minimum follow up was twelve months (12–96). Outcome data was available on 8/10 patients managed without reconstruction (WOR), with residual ilium collapsing back onto sacrum, and on 5/7 patients with bone graft reconstruction (WR).

Average age thirty-three years (WOR) and 48yrs (WR), (p=0.04), with average maximal tumour dimensions of 12cm and 9cm (p=0.1). The most frequent diagnosis was chondrosarcoma. The WOR group average TESS, MSTS 87 and MSTS 93 scores were respectively 73%, 18/35 and 58% at an average of 50 months (24–96) compared to 69%, 21/35 and 51% at an average of 37 months (12–60) for the WR group. 33% of WOR and 20% of WR patients did not require walking aids. Infection or wound necrosis occurred in 40% of WOR patients and 57% of WR patients. No local recurrences.

The perceived advantages of no reconstruction are shorter operating times, reduced incidence of complications and improved functional outcome due to medialization of the weightbearing axis in the absence of hip abductors. The oncologic/functional outcomes of both groups were similar but in those not reconstructed there was a lower incidence of complications and walking aids.

Purpose: Osteosarcoma (OS) is the most common type of cancer in children. OS demonstrates aggressive growth with a high risk of early, pulmonary metastasis. Here we investigated expression of malignancy-related factors in six osteosarcoma cell lines (SaOS, MNNG/ HOS, MG63, SW1353, SKES, SJSA), ten biopsies of primary OS and OS derived cells.

Methods: For this project, we are using RT-PCR and immunohistochemistry to detect PARP, ET-1, ETA and ETB receptor. We also, examined the expression of osteocrin by in situ hybridization. Zymography and Northern Blot were use to observe the presence of gela-tinases (MMP-2 and MMP-9) and finally, we showed the presence of ET-1(1–31) by Elisa-immunoassay.

Results: In OS tissues and cells, we observed ET-1, MMP-2, and ETA receptor overexpression, in contrast to under-expression of MMP-9 and ETB receptor. Additionally, in high malignant OS cells, MMP-2, MMP-3, MMP-13 and PARP were overexpressed and TIMP-1, TIMP-2 and TIMP-4 expressed at low levels. Using a new specific immunoassay for ET-1 (1–31) we showed presence of this alternative form of ET-1 in OS-derived cells. We also showed that, in cells exposed to ET-1, the inhibition of NF-kB pathway (NF-kB is an ubiquitous transcription factor playing a central role in differentiation, proliferation and malign transformation) drastically blocked MMP-2 production and activity, and that ET-1 induces NF-kB p65 unit translocation to the nucleus.

Conclusions: Thus, we concluded that expression of malignancy-related factors in parallel to the histological evaluation of these tumors, could be beneficial for malignancy understanding. Tumor cells invasion and aggressiveness of OS cells are the results, in part, of the tumorigenic potential of alternative forms of ET-1 generated by MMPs and enhanced in malignant microenvironment. These factors could be predictive for tumoral progression. Funding: Educational Grant from the Canadian Orthopaedic Foundation. Funding Parties: Canadian Orthopaedic Foundation (Carrol A. Laurin Award) and MENTOR program of CIHR

A prospective evaluation of the functional status and quality of life of patients undergoing surgery for long bone and acetabular metastases was performed. Sixty-nine patients were enrolled in the study. IM nailing and prosthetic replacement were the most common methods of treatment. Results were assessed using the MSTS 1987, MSTS 1993, TESS and SF-36 pre-op and then at six and twelve weeks post-op. There was a significant improvement in all of these parameters. The need for pain medication also decreased significantly. These results show surgical treatment of bone metastases can be benificial to patients with a short life expectancy.

The purpose of this study was to objectively assess the benefits of surgical treatment of bone metastases in the first three months post-operatively.

This is the first prospective study to evaluate the impact of surgery on the quality of life and function of patients burdened by metastases to the appendicular skeleton.

Sixty-nine patients gave their informed consent to be followed prospectively. Patients were administered the SF-36, MSTS 1987, MSTS 1993 and TESS questionnaires pre-op, at six weeks and three months post-op.

Average age was sixty-one years. Average follow-up was six months with 71% of patients deceased at the latest follow-up. Thirty-five patients had a pathological fracture and thirty-four had an impending fracture. IM Nailing was performed in thirty-six patients, prosthetic replacement in twenty and various other methods of stabilization in the thirteen other cases. Complications occurred in 25% of patients. There was a statistically significant improvement in the MSTS 1987 (from 13,6 to 22,8), MSTS 1993 (21,7 to 51,7), TESS (37,7 to 67,7) and pain medication use in the first three months post-op. SF-36 physical component scores improved significantly at six and twelve weeks while mental component scores improved significantly only at twelve weeks post-op.

Our data shows that surgical treatment of metastatic disease to long bones improves functional status and quality of life in a relatively short time frame. This is significant in a group of patients suffering from advanced neoplasia.

This study suggest interesting benefits in the overall well-being of patients treated surgically for bone metastases.

Funding: Funding was received from CHIR and FREOM.

Purpose: To determine the outcome of patients 80 years old and greater that were diagnosed with a primary soft tissue sarcoma and if these patients should be treated as aggressively as younger patients.

Methods: One-hundred two patients were retrospectively reviewed.Well differentiated liposarcoma and der-matofibrosarcoma were excluded.

Results: There were 52 males. Average age was 84 years (80–94). Malignant fibrous histiocytoma was most common (36 patients) followed by leiomyosarcoma (22 pts) and liposarcoma (17 pts). Tumors were superficial in 25 patients and deep in 75. The lower extremity was most frequent site(70 patients), 27 patients had upper extremity involvement and 9 had a back lesion. MSTS stages were IA 6 patients, IB 22 patients, IIA 55 patients, IIB 9 patients, III 1 patient, and was unknown for 9 cases. Lesions were larger than 5cm in 80%. Four patients had no surgery, 89 patients had limb salvage, and 8 patients underwent amputation. Thirty-two patients had pre-operative radiotherapy, 30 patients had post-operative radiation, and 3 patients received both. No patients were given chemotherapy. The average follow up was 24 months (0–107months). Seventeen patients experienced local recurrence. Thirty-one patients developed metastatic disease. At latest follow-up 49 patients were alive without disease, 21 patients were alive with disease, 22 patients died of their disease, 8 patients died of another cause and the final status was unknown for 2 patients.. The MSTS functional score pre-treatment was 24 (11–72) and 31 (20–77) one year following treatment.

Conclusions: Elderly patients with soft tissue sarcoma have a poor outcome. Taking into account their associated medical condition, this group should likely be managed as younger patients although chemotherapy has no role according to our experience Funding: Other Education Grant Funding Parties: CIHR,|Stryker Canada

This study was designed to be the first to prospectively evaluate CT-guided radiofrequency ablation for osteoid osteoma in terms of pain control, medication consumption, quality of life and patient function.

Over two years, forty patients with symptoms and radiographic findings classic for osteoid osteoma were offered radioablation. Patients were asked to fill out facial, subjective and visual analog pain scales and to undergo the Musculoskeletal Tumour Society 1987 functional assessment.

Results show immediate and lasting resolution of symptoms, a sharp drop in drug use and a significant improvement in function thus supporting the role of radioablation as first line therapy.

The purpose of this study was to prospectively evaluate the usefulness of radioablation for osteoid osteoma in terms of pain control, analgesic drug consumption, quality of life and patient function.

Radioablation appears to be a safe and effective method of treatment for osteoid osteoma. It offers immediate and lasting resolution of symptoms. Results support its role as first line therapy.

This is the first study to prospectively measure the outcome of patients treated with CT-guided radiofrequency ablation for osteoid osteoma.

The mean follow-up time is 6.93 months (sd: 6.51). All but seven procedures were done under regional anaesthesia. No complications were reported. 50% of core biopsy specimens were diagnostic of osteoid osteoma. The visual analog pain scale showed a value of 2.13(sd: 2.5) pre-op and 0.33(sd: 1.07) at 1 year (p=0.00033). The MSTS score rose from 28.86(sd: 4.68) pre-operatively to 34.06(sd: 1.95) after one year (p=0.000000049). Medication consumption was markedly reduced. All eighteen patients with more than one- year follow-up are drug free.

Over two years, forty patients with symptoms and radiographic findings classic for osteoid osteoma who had already received various treatments were offered radioablation. Written consent was obtained and patients were asked to fill out facial, subjective and visual analog pain scales. The Musculoskeletal Tumour Society 1987 functional assessment was performed. This data was collected two weeks prior to treatment and then at two weeks, three months and one year after treatment. The procedure was performed under CT guidance and on a one-day hospital admission basis.

A retrospective study was performed to evaluate the results of proximal humeral replacement prosthesis in the oncologic setting. Following tumour resection and implantation of the prosthesis, the soft tissues around the shoulder were either sutured directly to the prosthesis (three cases) or a dacron capsuloplasty was performed (five cases). Emphasis was on assessing shoulder instability. Eight patients were availaible for the study. Three patients needed to be re-operated for instability. Average instability rating on the ASES visual analog scale was 3,2/10. We conclude the prosthetic instability can be a significant problem for these patients.

The purpose of this study was to assess the results of oncologic proximal humeral prosthesis with a focus on shoulder instability.

Following limb-salvage procedures of the shoulder girdle, reconstruction of the soft-tissues to obtain prosthetic stability can be a major challenge.

A retrospective study of patients that underwent oncologic shoulder replacement. Results were evaluated using the SF-36 questionnaire, the MSTS 1987 and 1993 scales as well as the Standardized ASES method for assessement of shoulder function, including the visual analog scale for instability.

Nine patients were still living and eight of them were able to participate in this study. Average follow-up was seventy-three months. In five cases a capsuloplasty was performed using a dacron vascular prosthesis. In the remaining cases the capsule, rotator cuff or deltoid were sutured directly to the prosthesis.

Average instability rating was 3,2/10 using the visual analog scale. Three patients were reoperated for instability. Two had a failed soft tissue repair with inferior dislocation of the prosthesis and one had recurrent anterior dislocation.

Average MSTS 1987 and 1993 scores were 19,9 and 18,9 respectively.

SF-36 scores were significantly lower than Canadian standards in the physical functioning, role physical and mental health domains.

Our data show a significant rate of instability related problems following prosthetic replacement of the proximal humerus in cases of limb salvage. We were unable to indentify specific strategies to prevent this.

Further research is needed to determine optimal soft tissue reconstruction for oncologic procedure about the shoulder.